Bilateral 5 Hz transcranial alternating current stimulation on fronto-temporal areas modulates resting-state EEG

Rhythmic non-invasive brain stimulations are promising tools to modulate brain activity by entraining neural oscillations in specific cortical networks. The aim of the study was to assess the possibility to influence the neural circuits of the wake-sleep transition in awake subjects via a bilateral transcranial alternating current stimulation at 5 Hz (theta-tACS) on fronto-temporal areas. 25 healthy volunteers participated in two within-subject sessions (theta-tACS and sham), one week apart and in counterbalanced order. We assessed the stimulation effects on cortical EEG activity (28 derivations) and self-reported sleepiness (Karolinska Sleepiness Scale). theta-tACS induced significant increases of the theta activity in temporo-parieto-occipital areas and centro-frontal increases in the alpha activity compared to sham but failed to induce any online effect on sleepiness. Since the total energy delivered in the sham condition was much less than in the active theta-tACS, the current data are unable to isolate the specific effect of entrained theta oscillatory activity per se on sleepiness scores. On this basis, we concluded that theta-tACS modulated theta and alpha EEG activity with a topography consistent with high sleep pressure conditions. However, no causal relation can be traced on the basis of the current results between these rhythms and changes on sleepines

Using EEG measures to quantify reduced daytime vigilance in patients diagnosed with obstructive sleep apnoea using a novel electroencephalogram analysis method

Introduction Vigilance in obstructive sleep apnoea (OSA) does not correlate well with disease severity/ symptoms: Hence the need for a simple objective test. One such method could be quantitative analysis of the awake electroencephalogram (qEEG). qEEG is conventionally analysed using Power Spectral Analysis (PSA) looking at different EEG frequencies of delta, theta, alpha and beta. A novel method of analyzing the qEEG: De-trended fluctuation analysis (DFA) provides a single value: the scaling exponent (SE), which measures the fluctuations in the EEG signal. Artefact removal from qEEG is mandatory with the gold standard being manual scoring. Another method of automated artefact removal is independent component analysis (ICA). Objective Investigate the role of PSA and DFA (SE) as an objective measure of testing vigilance and validate the use of ICA in patients diagnosed with OSA. Methodology Retrospective cross-sectional study of untreated OSA patients. Results ICA and manual artefact removal gave well-correlated results in the DFA (SE), but not PSA. EEG slowing measured by PSA and DFA did not correlate to impaired performance during a battery of 14 separate performance tests. Conclusion ICA and manual artefact removal can be interchangeably used in extracting DFA measurements with confidence. In PSA metrics the use of ICA may not be reliable

Using EEG measures to quantify reduced daytime vigilance in patients diagnosed with obstructive sleep apnoea using a novel electroencephalogram analysis method

Introduction Vigilance in obstructive sleep apnoea (OSA) does not correlate well with disease severity/ symptoms: Hence the need for a simple objective test. One such method could be quantitative analysis of the awake electroencephalogram (qEEG). qEEG is conventionally analysed using Power Spectral Analysis (PSA) looking at different EEG frequencies of delta, theta, alpha and beta. A novel method of analyzing the qEEG: De-trended fluctuation analysis (DFA) provides a single value: the scaling exponent (SE), which measures the fluctuations in the EEG signal. Artefact removal from qEEG is mandatory with the gold standard being manual scoring. Another method of automated artefact removal is independent component analysis (ICA). Objective Investigate the role of PSA and DFA (SE) as an objective measure of testing vigilance and validate the use of ICA in patients diagnosed with OSA. Methodology Retrospective cross-sectional study of untreated OSA patients. Results ICA and manual artefact removal gave well-correlated results in the DFA (SE), but not PSA. EEG slowing measured by PSA and DFA did not correlate to impaired performance during a battery of 14 separate performance tests. Conclusion ICA and manual artefact removal can be interchangeably used in extracting DFA measurements with confidence. In PSA metrics the use of ICA may not be reliable

Neuroanatomical correlates of cognitive dysfunction in obstructive sleep apnoea

Obstructive sleep apnoea (OSA) has been reported to be associated with brain hypotrophy and cognitive dysfunction; however, whether these normalise after treatment is unclear. The overall aim of this thesis is to investigate the relationship between OSA and brain structure using FreeSurfer (a new automated technique that reliably measures brain structures). I have investigated changes in brain morphology and the newly described phenomenon in OSA of ischaemic preconditioning. Chapters 4 and 5 will also assess brain structural response to CPAP, and investigate the association between brain structure and cognitive function in OSA. Chapter 3 reports an observational study investigating brain structure. FreeSurfer analysis of magnetic resonance imaging (MRI) found OSA patients had hypertrophy in the right hippocampus (p=0.03) and right choroid plexus (p=0.02) but hypotrophy of the corpus callosum (p=0.04) compared to healthy controls. Chapter 4 reports a randomised controlled trial of CPAP in OSA. At baseline hypotrophy was seen in the corpus callosum (p=0.03) and pallidum (p=0.03) of OSA patients compared to healthy controls. Hypertrophic changes in the right thalamus were seen in the CPAP group after 1 month (p=0.06), associated with improvement in verbal memory (p=0.04). Chapter 5 reports a randomised controlled trial of CPAP in older patients with OSA. A significant decrease in left fimbria volume was seen in the CPAP group (p=0.01). A significant increase in the left presubiculum volume was seen in the best supportive care group (p=0.03). No hippocampal hypertrophy was seen in the CPAP group. In summary, young and middle-aged OSA patients had evidence of brain hypotrophy, but also areas of hypertrophy that may signify dendritic sprouting and increased connectivity as a result of ischaemic preconditioning. This allows recovery of brain hypotrophy after CPAP treatment. This was not seen in older OSA patients suggesting an age-related difference which may have implications for OSA treatment in older people.Open Acces

The effects of nap duration on sleep inertia and physical performance

PURPOSE: To assess the effects of 15 and 30-min naps on 3-km time trial performance and peak muscle strength. METHODS: Six recreationally trained college-aged participants visited the lab on 4 separate occasions. During each visit, participants completed a peak strength test, and a 3-km time trial following the nap condition. For the muscle strength test, peak isokinetic leg extension strength was assessed. The 3-km time trial was computer simulated time of completion and average power output was recorded. Nap conditions were: no-nap, 15-minute nap, and 30-minute nap. One-Way (nap condition) and Repeated Measures ANOVA’s (time x nap condition) were used to statistically analyze the data, with the level of significance set at pRESULTS: Neither the 15 or 30-minute nap had an impact on 3-km time trial finishing time or average power output when compared to the no nap condition. Though it did not reach statistical significance, peak strength tended to be impaired by the 30-min nap when compared to the 15-min nap (p=.075). CONCLUSION: A 15- or 30-minute nap has no effect on 3-km time trial finishing time, average power output, or peak strength performance, suggesting that napping prior to competition will not improve performance. Data should be gathered on a larger sample size and with naps of longer duration to definitively conclude that napping has no impact on performance

Fatigue bei unipolarer Depression, immunologischen und (neuro-) inflammatorischen Erkrankungen: die Rolle des ZNS-Arousal

Pathologische Fatigue wird von PatientInnen mit einem breiten Spektrum immunologischer, (neuro-) inflammatorischer und psychiatrischer Erkrankungen berichtet. Dabei kann Fatigue sowohl ein Zustand ausgeprägter Tagesschläfrigkeit, Energie- und Antrieblosigkeit sein (i.S.v. sickness behavior; häufig beobachtet im Kontext immunologischer und (neuro-)inflammatorischer Prozesse), als auch ein Zustand der Erschöpfung mit einer hohen inneren Anspannung, Antriebshemmung und Einschlafstörungen, welcher typisch für unipolare Depression ist. Um diese auf der physiologischen Ebene diametral entgegengesetzten Zustände auseinanderzuhalten, wurde eine Unterteilung in Fatigue mit Hypoarousal und Fatigue mit Hyperarousal vorgeschlagen (Hegerl et al., 2013). Die zugrundeliegenden Unterschiede des ZNS-Arousal und seiner Regulation können objektiv mittels EEG erfasst werden. Das ZNS-Arousal bildet ein Spektrum globaler Hirnfunktionszustände, die auf der Verhaltensebene von angespannter Wachheit über Ruhewachzustand und Dösigkeit bis in den Tiefschlaf reichen und auf der elektrophysiologischen Ebene unterschiedlichen EEG-Vigilanzstadien entsprechen. Die Mehrheit der gesunden ProbandInnen zeigt während eines 15-minütigen Ruhe-EEG mit geschlossenen Augen einen kontinuierlichen Abfall der Vigilanzstadien bis hin zum Einschlafen; nur wenige verbleiben in höheren Vigilanzstadien oder zeigen einen raschen Abfall in niedrige Stadien. Demgegenüber verbleiben depressive PatientInnen deutlich länger in höheren Vigilanzstadien (hyperstabile Arousalregulation), während bei PatientInnen mit tumorbedingter Fatigue niedrigere Vigilanzstadien früher und häufiger auftreten als bei gesunden Kontrollen (instabile Arousalregulation). Publikation 1: Mehr als 90% der PatientInnen klagen über schwere Fatigue während einer depressiven Episode. Zugleich weist eine Vielzahl klinischer und neurophysiologischer Studien auf eine Assoziation zwischen unipolaren Depressionen und ZNS-Hyperarousal hin – neben der hyperstabilen Arousalregulation gehören auch Hyperaktivität der HPA-Achse und abweichende ANS-Parameter zu den typischen Befunden. Mehrheitlich berichten diese PatientInnen von Schwierigkeiten beim Ein- und Durchschlafen und Müdigkeit im Sinne von Erschöpfung bei innerer Daueranspannung. Gleichwohl werden von einem Teil der PatientInnen verlängerte Schlafzeiten und/oder exzessive Tagesschläfrigkeit angegeben, und während einer Ruhe-EEG-Messung mit geschlossenen Augen erreicht nur ein geringer Anteil niedrige Vigilanzstadien (Hypoarousal). Fragestellung: unterscheiden sich PatientInnen mit Fatigue und mit Hypoarousal hinsichtlich der depressiven Symptomatik von denen ohne Hypoarousal? Methode: Es wurden retrospektive Daten von 102 Patienten mit Fatigue während einer depressiven Episode analysiert. Nach Auswertung der 15-minütigen Ruhe-EEG-Messungen mittels VIGALL 2.1 erfolgte die Zuteilung in Gruppen mit oder ohne ZNS-Hypoarousal welche danach hinsichtlich ihrer Angaben zu Fatigue, depressiven Symptomatik, „trait“ und „state“ Tagesschläfrigkeit und Schlafqualität verglichen worden sind. Ergebnis: Trotz ausgeprägter Fatigue zeigten nur 23.5% Anzeichen der Dösigkeit oder des Schlafbeginns nach 15 Minuten unter schlaffördernden Bedingungen. Was bei doppelt so vielen gesunden ProbandInnen (48,3%; Hegerl, Wilk et al., 2012) und sogar bei 59% einer Patientenstichprobe mit ähnlich schwerer tumorbedingter Fatigue beobachtet wurde (Olbrich et al., 2012). Dass der Rest der Stichprobe in höheren Vigilanz Stadien verblieb, bekräftigte erneut den Befund einer hyperstabilen Arousalregulation bei Depression. Die Gruppe mit Hypoarousal hatte signifikant höhere „state“ und „trait“ Schläfrigkeit, beklagte größere Konzentrationsschwierigkeiten (BDI-II), mehr Energieverlust (BDI-II), und stärkere kognitive Fatigue (MFI-20). Die erfasste Instabilität der Arousalregulation könnte Konzentrationsschwierigkeiten und die damit zusammenhängende kognitive Fatigue erklären. Stärker ausgeprägte Energielosigkeit steht im Einklang mit dem Modell von Hegerl und Ulke (2016), demnach das ZNS-Hypoarousal mit Antriebsmangel und ZNS-Hyperarousal mit Antriebshemmung einhergehen. Demgegenüber waren suizidale Gedanken marginal häufiger (BDI-II; p=.051) in der Gruppe ohne Hypoarousal und eine exploratorische partielle Korrelationsanalyse ergab einen signifikanten Zusammenhang (rho=.27, p=.018) zwischen ZNS-Arousal und dem Auftreten der Selbstmordgedanken, wenn Alter, Geschlecht und BDI-II Gesamtwert als Kontrollvariablen berücksichtigt wurden. Dieser Befund bekräftigt die Rolle des ZNS-Hyperarousal in der Pathophysiologie der suizidalen Gedanken. Publikation 2: Fatigue gehört zu den häufigsten Symptomen einer ganzen Reihe immunologischer und (neuro-) inflammatorischer Erkrankungen wie Krebs, rheumatische Erkrankungen, Morbus Parkinson, Multiple Sklerose. Verschiedene Indikatoren des ZNS-Hypoarousal wie exzessive Tagesschläfrigkeit, kurze Einschlaflatenzen, instabile Arousalregulation und Unterfunktion der HPA-Achse wurden für mehrere dieser Krankheiten aufgezeigt. Gleichzeitig weisen diese Erkrankungen hohe Komorbiditäten zu Depression auf. Fragestellung: Ist bei PatientInnen mit immunologischen/(neuro-)inflammatorischen Erkrankungen und Fatigue das ZNS-Hyperarousal mit höheren Depressionswerten assoziiert? Methode: Daten von 60 ProbandInnen mit Krebs, neuroinflammatorischen und autoimmunen Erkrankungen aus der 60+LIFE Kohorte der LIFE-Adult Studie wurden analysiert. Nach Auswertung der 20-minütigen Ruhe-EEG-Messungen erfolgten Gruppenzuteilung und Vergleich hinsichtlich Fatigue, depressiven Symptomatik, „trait“ Tagesschläfrigkeit und subjektiven Schlafqualität. Ergebnis: Die Gruppe mit ZNS-Hyperarousal erzielte signifikant höhere Depressionswerte, welche vor allem durch depressionstypische Symptome wie z.B. verlängerte Einschlaflatenzen, Niedergeschlagenheit und Anspannung zustande kamen, und nicht lediglich durch Symptome der somatischen Erkrankungen selbst wie z.B. Schmerz oder negative Sicht auf die Zukunft. Obwohl ProbandInnen mit einer aktuellen depressiven Episode ausgeschlossen worden waren, berichteten 7% der Gesamtstichprobe von moderaten bis schweren depressiven Symptomen, weitere 53% gaben leichte depressive Symptome an. Die im Kontext einer depressiven Episode bereits mehrfach bestätigte Assoziation zwischen dem ZNS-Hyperarousal und der depressiven Symptomatik könnte somit bereits im subklinischen Bereich existieren. Die Ergebnisse der vorliegenden Dissertation untermauern die Validität einer ZNS-Arousal geleiteten Differenzierung zweier Fatigue-Subtypen. Studien zur Pathophysiologie der Fatigue und Wirksamkeit therapeutischer Interventionen könnten durch die Berücksichtigung des generalisierten ZNS-Arousal höhere Homogenität innerhalb der Patientengruppen erzielen. Ebenfalls konnte die Rolle des ZNS-Hyperarousal als Marker der Depression wiederholt bestätigt werden.:Inhaltsverzeichnis Abkürzungsverzeichnis 1 Einleitung 1.1 Zwei Gesichter der Fatigue 1.2 Theoretisches Modell der Arousalregulation des zentralen Nervensystems 1.3 Der Vigilanz Algorithmus Leipzig 1.4 Fatigue und Arousal im Kontext der unipolaren Depression 1.5 Fatigue und Arousal im Kontext immunologischer und (neuro-)inflammatorischer Erkrankungen 1.6 Klinische Relevanz der Differenzierung von zwei Fatigue-Subtypen 1.7 Fragestellungen der vorliegenden Arbeit 2 Publikationen 2.1 Publikation 1 2.2 Publikation 2 3 Zusammenfassung der Arbeit 4 Literaturverzeichnis 5 Darstellung des eigenen Beitrags 6 Selbstständigkeitserklärung 7 Lebenslauf und wissenschaftlicher Werdegang 8 Danksagun

Uloga aktivacijskoga sustava u regulaciji pospanosti

Sleepiness is a widespread phenomenon in the busy industrial countries, and many studies have identified its significant negative impacts on individuals and society. Particularly important are the data that associate sleepiness with the risk of accidents at workplace and in transport, pointing to shift workers as the most vulnerable population. It is generally accepted that two basic physiological processes regulate sleepiness: homeostatic and circadian rhythmic processes. Recent research has proposed the third component regulating sleepiness, that is, the wake drive or the arousal system. The role of the arousal system in regulating sleepiness has partly been addressed by the studies of the pathophysiology of insomnia, which is often described as a disorder of hyperarousal. Experimental and correlational studies on the relation between sleepiness and arousal in good sleepers have generally indicated that both physiological and cognitive arousal are related to the standard measures of sleepiness. Taking into account the role of the arousal system in regulating sleepiness widens the possibilities for the management of sleep disorders and could also help in solving the problem of excessive sleepiness at work and the wheel.Pospanost je raširena pojava u industrijskim zemljama i njeni negativni učinci na pojedince i društvo ustanovljeni su u brojnim istraživanjima. Od posebne su važnosti podaci koji upućuju na to da pospanost povećava vjerojatnost nesreća na radu i u prometu, što je naročito izraženo u populaciji smjenskih radnika. Općenito je prihvaćeno da pospanost reguliraju dva temeljna fiziološka procesa, od koji se jedan odnosi na homeostazu spavanja, a drugi na cirkadijurno funkcioniranje organizma. Nedavno objavljeni modeli pospanosti predložili su uključivanje nagona za budnošću, odnosno razine aktivacije, kao trećeg čimbenika koji sudjeluje u regulaciji pospanosti. Ideje o važnosti aktivacijskog sustava u regulaciji pospanosti dijelom su proizašle iz ispitivanja patofiziologije nesanice koja se često opisuje kao poremećaj pretjerane pobuđenosti. Eksperimentalna i korelacijska istraživanja odnosa između pospanosti i aktivacije kod dobrih spavača općenito su pokazala kako su fiziološka i kognitivna aktivacija povezane sa standardnim mjerama pospanosti. Uvažavanje aktivacijskog sustava u regulaciji pospanosti otvara šire mogućnosti za rješavanje problema sa spavanjem te bi također moglo pomoći u rješavanju problema pretjerane pospanosti u različitim radnim okruženjima i prometu

A Craniofacial Morphology Study Of Patients With Obstructive Sleep Apnea

Masalah tidur obstruktif apnea (OSA) didefinisikan sebagai pemberhentian pernafasan berulang (apneas) yang berlaku sekurang-kurangnya selama sepuluh saat atau lebih pada sesuatu ketika semasa tidur. Obstructive sleep apnea (OSA) is defined as a repetitive cessations of breathing (apneas) lasting for at least 10 seconds or more for each event during sleep

What Happened Last Night? Sleep, Sex, and Recollection

Previous research has repeatedly illustrated the beneficial influence of sleep on memory processes. Further, evidence has demonstrated the power of sexual valance to enhance memory for certain types of stimuli. The present study investigated the possible interaction effect between sleep and sexual valance on recollection memory in 44 undergraduate and graduate student participants at Eastern Kentucky University, based upon a method by Alger, Lau, & Fishbein (2012); however, in the current study, recollection memory items were words received audibly rather than visually. Behavioral data, electroencephalography (EEG), and skin conductance data was collected to assess memory performance, sleep progress, autonomic nervous system activity, and sleep-related behavior. Results indicated a significant interaction effect between condition (sleep/awake) and image type (sexual/nonsexual): words paired with sexual images were best recalled by sleep participants, while awake participants recalled nonsexual images better than sexual images

Orexin and Psychoneurobiology: A Hidden Treasure

Orexin is a neuropeptide secreted from the lateral hypothalamus and prefrontal cortex concerned in wakefulness and excitement. This study aimed to review the possible neurobiological effect of orexin. A diversity of search strategies was adopted and assumed which included electronic database searches of Medline and PubMed using MeSH terms, keywords, and title words. Orexin plays a vital role in activation of learning, memory acquisition, and consolidation through activation of the monoaminergic system, which affects cognitive flexibility and cognitive function. Orexin stimulates adrenocorticotrophin (ACTH) and corticosteroid secretions via activation of the central corticotropin-releasing hormone (CRH). Cerebrospinal (CSF) and serum orexin serum levels are reduced in depression, schizophrenia, and narcolepsy. However, high orexin serum levels are revealed in drug addictions. Regarding neurodegenerative brain diseases, CSF and serum orexin levels are reduced in Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Orexin antagonist leads to significant reduction of sympathetic overactivity during withdrawal syndrome. Also, orexin antagonist improves sleep pattern. The orexinergic system is involved in different psychiatric and neurological disorders; therefore targeting of this system could be a possible novel pathway in the management of these disorders. In addition measurement of CSF and serum orexin levels might predict the relapse and withdrawal of addict patients